Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial.

BACKGROUND: 2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth. METHODS: This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022. FINDINGS: 37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio [aOR] 0·90, 95% CI 0·75-1·07; p=0·23). INTERPRETATION: The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven. FUNDING: Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.

Guidance for withdrawal and withholding of intensive care as part of neonatal end-of-life care.

INTRODUCTION: Advances in foetal medicine and neonatology have enabled increased antenatal diagnosis of life-limiting conditions and improved preterm survival, escalating the debate surrounding the ethics of neonatal end-of-life care and withholding or withdrawing intensive care. SOURCES OF DATA: Literature search of MEDLINE and the Cochrane library databases using the search terms [neonatal palliative care] AND [neonatal AND withdrawal of intensive care and treatment]. Review of consensus statements and guidelines. AREAS OF AGREEMENT: UK practice is aided by Grade 3-4 evidence, consensus statements and practice frameworks. There is limited systematic evidence. AREAS OF CONTROVERSY: We illustrate UK practice with clinical cases and describe worldwide variations. GROWING POINTS: Neonatal end-of-life care incorporating withholding and withdrawing intensive care is not uncommon. The child's 'best interests' take precedent and clinical guidance has been published to support the joint decision-making partnership of clinicians and families. Withholding and withdrawing intensive care should be part of an overall end-of-life care plan incorporating the principles and standards of palliative care. AREAS TIMELY FOR DEVELOPING RESEARCH: Further guidance on standards and staff training with regard to communicating and delivering neonatal end-of-life care is required to ensure consistent practice of staff and choices for families. The recommended establishment of neonatal outcome databases should aid UK preterm decision-making (NHS and Department of Health Neonatal Taskforce, Toolkit for high-quality neonatal services, London, Department of Health 2009).

Can promoting awareness of fetal movements and focusing interventions reduce fetal mortality? A stepped-wedge cluster randomised trial (AFFIRM).

BACKGROUND: In 2013, the stillbirth rate in the UK was 4.2 per 1000 live births, ranking 24th out of 49 high-income countries, with an annual rate of reduction of only 1.4% per year. The majority of stillbirths occur in normally formed infants, with (retrospective) evidence of placental insufficiency the most common clinical finding. Maternal perception of reduced fetal movements (RFM) is associated with placental insufficiency and increased risk of subsequent stillbirth.This study will test the hypothesis that the introduction of a package of care to increase women's awareness of the need for prompt reporting of RFM and standardised management to identify fetal compromise with timely delivery in confirmed cases, will reduce the rate of stillbirth. Following the introduction of a similar intervention in Norway the odds of stillbirth fell by 30%, but the efficacy of this intervention (and possible adverse effects and implications for service delivery) has not been tested in a randomised trial. METHODS: We describe a stepped-wedge cluster trial design, in which participating hospitals in the UK and Ireland will be randomised to the timing of introduction of the care package. Outcomes (including the primary outcome of stillbirth) will be derived from detailed routinely collected maternity data, allowing us to robustly test our hypothesis. The degree of implementation of the intervention will be assessed in each site. A nested qualitative study will examine the acceptability of the intervention to women and healthcare providers and identify process issues including barriers to implementation. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Scotland A Research Ethics Committee (Ref 13/SS/0001) and from Research and Development offices in participating maternity units. The study started in February 2014 and delivery of the intervention completed in December 2016. Results of the study will be submitted for publication in peer-reviewed journals and disseminated to local investigating sites to inform education and care of women presenting with RFM. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov NCT01777022. VERSION: Protocol Version 4.2, 3 February 2017.

Defining the relationship between fetal Doppler indices, abdominal circumference and growth rate in severe fetal growth restriction using functional linear discriminant analysis.

The relationship between Doppler measurements, size and growth rate in fetal growth restriction has not been defined. We used functional linear discriminant analysis (FLDA) to investigate these parameters taking account of the difficulties inherent in exploring relationships between repeated observations from a small number of cases. In 40 fetuses with severe growth restriction, serial abdominal circumference (AC), umbilical, middle cerebral artery (MCA) and ductus venosus Doppler pulsatility index measurements were recorded. In 11 singleton fetuses with normal growth, umbilical artery pulsatility index only was measured. Data were expressed as z-scores in relation to gestation and analysed longitudinally using FLDA. In severe growth restriction, the Spearman correlation coefficients between umbilical artery pulsatility index and AC z-score, MCA pulsatility index and AC z-score and ductus venosus pulsatility index z-score and AC z-score were, respectively: -0.36, p = 4.4 × 10(-7); 0.70, p = 1.1 × 10(-17) and -0.50, p = 8.1 × 10(-4). No relationship was seen between Doppler parameters and growth rate. There was no relationship between umbilical artery pulsatility index and AC nor growth rate in normally grown fetuses. In severe fetal growth restriction, Doppler changes are related to absolute fetal AC size, not growth rate.

Relationship between placental morphology and histological findings in an unselected population near term.

Whilst individual histological features are well described, there are no universally agreed criteria as to what constitutes a clinically significant histological lesion of the placenta in an uncomplicated pregnancy, nor has the presence of such histological findings been systematically related to quantitative morphological characteristics of the placenta (such as placental shape, cord insertion and cord coiling). This study aims to explore this relationship and further to describe the incidence of predefined categories of histological lesions of the placenta in an unselected obstetric population recruited prior to delivery. The study is based upon the placental examination of 1,156 women with singleton pregnancies recruited prospectively in a single unit. Placentas were analysed where deliveries occurred between 34-43 weeks. The incidence of normal histological findings and specific histological categories, such as ascending genital tract infection, chronic placental underperfusion, intervillous thrombus and villitis of unknown aetiology, were noted. The relationship between placental morphological indices: coiling index, cord centrality index (distance of cord insertion on the chorionic plate from the centre) and eccentricity (shape of the placenta) and histological lesions was investigated. There were no significant differences between cord centrality and eccentricity between placentas with and without histological lesions except an association between hypercoiling of the umbilical cord and intervillous thrombosis and villitis of unknown aetiology (p = 0.024 and p = 0.009, respectively). The macroscopic morphological features of the placenta cannot predict the presence or absence of the histological placental lesions, nor are these lesions in general associated with differences in cord centrality, placental eccentricity or cord coiling.

Obstetric and neonatal outcomes in severe fetal ventriculomegaly.

OBJECTIVE: To determine the early outcome and the incidence of associated structural anomalies in pregnancies complicated by severe fetal ventriculomegaly (VM). METHODS: A review of cases of severe fetal VM (posterior horn of lateral ventricle > 15 mm at referral or during prenatal follow-up) referred to a fetal medicine centre in Eastern England over 4 years from 2001 was made. Results of specialist prenatal investigations including ultrasound (US), karyotype, antiplatelet antibodies and congenital infection screen were noted. Neonatal clinical and cranial US findings, autopsy findings and neurodevelopmental follow-up at 4 months were obtained. RESULTS: Twenty cases of severe VM were identified, including 3 with spina bifida. Median gestation at diagnosis was 28 weeks (range 16-36 weeks). Twelve cases had additional intra-cranial abnormalities and two had abnormalities outside the central nervous system. One case was complicated by toxoplasmosis. There was one case of trisomy 21. Ten pregnancies were terminated. Ten babies were live born, all of whom had VM confirmed, and two of these babies died within 4 months. Of the remaining eight, seven have abnormal neurodevelopment. CONCLUSIONS: Severe VM is often diagnosed after the threshold of viability. Termination of pregnancy was requested in about half the cases owing to the risk of long-term neurodisability, and in all cases diagnosed before 24 weeks. In those live born, there was abnormal outcome in all but one.

Doppler flow velocimetry in the superior mesenteric artery on the first day of life in preterm infants and the risk of neonatal necrotizing enterocolitis.

OBJECTIVE: The purpose of this work was to relate Doppler indices of splanchnic perfusion and vascular resistance to the risk of developing necrotizing enterocolitis. METHODS: We conducted a prospective cohort study with analysis of Doppler flow velocity waveforms of splanchnic vessels on the first day of life. Clinical management and diagnosis of necrotizing enterocolitis were performed blind to the Doppler results in a tertiary NICU on 64 eligible preterm neonates admitted for intensive care. We measured necrotizing enterocolitis using an objective diagnostic classification. RESULTS: When adjusted for gestational age at birth, the following indices of the Doppler flow velocity wave form in the superior mesenteric artery were significantly predictive of the risk of necrotizing enterocolitis: end-diastolic velocity, mean velocity, and pulsatility index. The association between necrotizing enterocolitis and Doppler velocimetry indicative of high vascular resistance was independent of a range of other factors and comorbidities (race, mode of delivery, umbilical arterial catheter, growth restriction, patent ductus arteriosus, jaundice, respiratory distress syndrome, mechanical ventilation, and hypotension). CONCLUSIONS: We concluded that neonates with high resistance patterns of blood flow velocity in the superior mesenteric artery on the first day of life are at increased risk of developing necrotizing enterocolitis.

Obstetric and neonatal outcomes in apparently isolated mild fetal ventriculomegaly.

AIMS AND METHODS: To determine obstetrical and neonatal outcomes in referrals of apparently isolated mild ventriculomegaly following routine ultrasound scan, over the period 2001-2003. Specialist ultrasound and other investigations were performed. Neonatal examination and postnatal ultrasound findings were collected and local neurodevelopmental follow-up was obtained. RESULTS: 30 cases of suspected isolated mild ventriculomegaly (posterior horn of lateral ventricle 10-15 mm at diagnosis) were identified. There were two abnormal karyotypes, no abnormal TORCH screens, and only one false-positive alloimmune thrombocytopenia screen. In 21 cases, isolated ventriculomegaly was confirmed following specialist investigation. In 11 of 21 cases, ventriculomegaly resolved during antenatal follow-up, and in one case it progressed. Six of 21 had ventriculomegaly confirmed on postnatal ultrasound and lissencephaly was diagnosed in one following postnatal MRI. Of the 11 infants with antenatal resolution of ventriculomegaly, 2 have delayed development. The infant with progressive ventriculomegaly has severe developmental problems.